Ginger extract activates caspase independent paraptosis in cancer cells via ER stress, mitochondrial dysfunction, AIF translocation and DNA damage

References

• Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495–516.
   PubMed Web of Science ®Google Scholar
• Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53(1):615–627.
   PubMed Web of Science ®Google Scholar
• Chalakur-Ramireddy NKR, Pakala SB. Combined drug therapeutic strategies for the effective treatment of triple negative breast cancer. Biosci Rep. 2018;38(1):BSR20171357.
   PubMed Web of Science ®Google Scholar
• Tsvetkova E, Goss GD. Drug resistance and its significance for treatment decisions in non-small-cell lung cancer. Curr Oncol. 2012;19:S45–S51.
   PubMed Web of Science ®Google Scholar
• Chipuk JE, Green DR. Do inducers of apoptosis trigger caspase-independent cell death?. Nat Rev Mol Cell Biol. 2005;6(3):268–275.
   PubMed Web of Science ®Google Scholar
• Sperandio S, de Belle I, Bredesen DE. An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci United States Am. 2000;97(26):14376–14381.
   PubMed Web of Science ®Google Scholar
• Xue J, Li R, Zhao X, Ma C, Lv X, Liu L, Liu P. Morusin induces paraptosis-like cell death through mitochondrial calcium overload and dysfunction in epithelial ovarian cancer. Chem Interact. 2018;283:59–74.
   PubMed Web of Science ®Google Scholar
• Nedungadi D, Binoy A, Pandurangan N, Pal S, Nair BG, Mishra N. 6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition. Exp Cell Res. 2018;364(2):243–251.
   PubMed Web of Science ®Google Scholar
• Seo MJ, Lee DM, Kim IY, Lee D, Choi M-K, Lee J-Y, Park SS, Jeong S-Y, Choi EK, Choi KS, et al. Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis. Cell Death Dis. 2019;10(3):187:
   PubMed Web of Science ®Google Scholar
• Binoy A, Nedungadi D, Katiyar N, Bose C, Shankarappa SA, Nair BG, Mishra N. Plumbagin induces paraptosis in cancer cells by disrupting the sulfhydryl homeostasis and proteasomal function. Chem Interact. 2019;310:108733.
   PubMed Web of Science ®Google Scholar
• Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc. 2008;46(2):409–420.
   PubMed Web of Science ®Google Scholar
• Shukla Y, Singh M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc. 2007;45(5):683–690.
   PubMed Web of Science ®Google Scholar
• Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013;145(1):146–151.
   PubMed Web of Science ®Google Scholar
• Mansingh DP, Pradhan S, Biswas D, Barathidasan R, Vasanthi HR. Palliative role of aqueous ginger extract on -nitroso–methylurea-induced gastric cancer. Nutr Cancer. 2019;1:1–13.
   Web of Science ®Google Scholar
• Elkady AI, Abuzinadah OA, Baeshen NA, Rahmy TR. Differential control of growth, apoptotic activity, and gene expression in human breast cancer cells by extracts derived from medicinal herbs Zingiber officinale. J Biomed Biotechnol. 2012;2012:614356
   PubMed Web of Science ®Google Scholar
• Karna P, Chagani S, Gundala SR, Rida PCG, Asif G, Sharma V, Gupta MV, Aneja R. Benefits of whole ginger extract in prostate cancer. Br J Nutr. 2012;107(4):473–484.
   PubMed Web of Science ®Google Scholar
• Liu Y, Whelan RJ, Pattnaik BR, Ludwig K, Subudhi E, Rowland H, Claussen N, Zucker N, Uppal S, Kushner DM, et al. Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53. PloS One. 2012;7(12):e53178.
   PubMed Web of Science ®Google Scholar
• Akimoto M, Iizuka M, Kanematsu R, Yoshida M, Takenaga K. Anticancer effect of ginger extract against pancreatic cancer cells mainly through reactive oxygen species-mediated autotic cell death. PloS One. 2015;10(5):e0126605.
   PubMed Web of Science ®Google Scholar
• Tuntiwechapikul W, Taka T, Songsomboon C, Kaewtunjai N, Imsumran A, Makonkawkeyoon L, Pompimon W, Lee TR. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells. J Med Food. 2010;13(6):1347–1354.
   PubMed Web of Science ®Google Scholar
• Gundala SR, Mukkavilli R, Yang C, Yadav P, Tandon V, Vangala S, Prakash S, Aneja R. Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract. Carcinogenesis. 2014;35(6):1320–1329.
   PubMed Web of Science ®Google Scholar
• Mukkavilli R, Yang C, Tanwar RS, Saxena R, Gundala SR, et al. Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent. Sci Rep. 2018;8:3056.
   PubMed Web of Science ®Google Scholar
• Prasad S, Tyagi AK. Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Pract. 2015;2015:142979
   PubMed Web of Science ®Google Scholar
• Semwal RB, Semwal DK, Combrinck S, Viljoen AM. Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry. 2015;117:554–568.
   PubMed Web of Science ®Google Scholar
• Jolad SD, Lantz RC, Chen GJ, Bates RB, Timmermann BN. Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochemistry. 2005;66(13):1614–1635.
   PubMed Web of Science ®Google Scholar
• Gan F-F, Nagle AA, Ang X, Ho OH, Tan S-H, Yang H, Chui W-K, Chew E-H. Shogaols at proapoptotic concentrations induce G(2)/M arrest and aberrant mitotic cell death associated with tubulin aggregation. Apoptosis: Int J Program Cell Death. 2011;16(8):856–867.
   PubMed Web of Science ®Google Scholar
• Ok S, Jeong W-S. Optimization of extraction conditions for the 6-shogaol-rich extract from ginger (Zingiber officinale Roscoe). Preventive Nutr Food Sci. 2012;17(2):166–171.
   PubMedGoogle Scholar
• Cheng X-L, Liu Q, Peng Y-B, Qi L-W, Li P. Steamed ginger (Zingiber officinale): changed chemical profile and increased anticancer potential. Food Chem. 2011;129(4):1785–1792.
   Web of Science ®Google Scholar
• Sharif MF, Bennett MT. The effect of different methods and solvents on the extraction of polyphenols in ginger (Zingiber officinale). J Teknol. 2016;78:49–54.
   Web of Science ®Google Scholar
• Shubin AV, Demidyuk IV, Komissarov AA, Rafieva LM, Kostrov SV. Cytoplasmic vacuolization in cell death and survival. Oncotarget. 2016;7(34):55863–55889.
   PubMed Web of Science ®Google Scholar
• Maltese WA, Overmeyer JH. Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome and endosome compartments. Am J Pathol. 2014;184(6):1630–1642.
   PubMed Web of Science ®Google Scholar
• Lee D, Kim IY, Saha S, Choi KS. Paraptosis in the anti-cancer arsenal of natural products. Pharmacol Ther. 2016;162:120–133.
   PubMed Web of Science ®Google Scholar
• Bak M-J, Ok S, Jun M, Jeong W-S. 6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice. Mol. 2012;17(7):8037–8055.
   PubMed Web of Science ®Google Scholar
• Wang Y, Li X, Wang L, Ding P, Zhang Y, et al. An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression. J Cell Sci. 2004;117(8):1525–1532.
   PubMed Web of Science ®Google Scholar
• Weinberg JM, Saikumar P. Mitochondrial function. Methods Mol Med. 2003;86:351–371.
   PubMedGoogle Scholar
• Kar R, Singha PK, Venkatachalam MA, Saikumar P. Saikumar P: a novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells. Oncogene. 2009;28(28):2556–2568.
   PubMed Web of Science ®Google Scholar
• Gupta S, Kass GEN, Szegezdi E, Joseph B. The mitochondrial death pathway: a promising therapeutic target in diseases. J Cell Mol Med. 2009;13(6):1004–1033.
   PubMed Web of Science ®Google Scholar
• Hong SJ, Dawson TM, Dawson VL. Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling. Trends Pharmacol Sci. 2004;25(5):259–264.
   PubMed Web of Science ®Google Scholar
• Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830(6):3670–3695.
   PubMed Web of Science ®Google Scholar
• Zheng H, Dong Y, Li L, Sun B, Liu L, Yuan H, Lou H. Novel benzo[a]quinolizidine analogs induce cancer cell death through paraptosis and apoptosis. J Med Chem. 2016;59(10):5063–5076.
   PubMed Web of Science ®Google Scholar
• Wasik AM, Almestrand S, Wang X, Hultenby K, Dackland Å-L. WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. Cell Death Dis. 2011;2:e225.
   PubMed Web of Science ®Google Scholar
• Zhang C, Jiang Y, Zhang J, Huang J, Wang J. 8-p-hdroxybenzoyl tovarol induces paraptosis like cell death and protective autophagy in human cervical cancer HeLa cells. Int J Mol Sci. 2015;16(12):14979–14996.
   PubMed Web of Science ®Google Scholar
• Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis: Int J Program Cell Death. 2003;8(2):115–128.
   PubMed Web of Science ®Google Scholar
• Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, Babenko VA, Zorov SD, Balakireva AV, Juhaszova M, et al. Mitochondrial membrane potential. Anal Biochem. 2018;552:50–59.
   PubMed Web of Science ®Google Scholar
• Richter C, Schweizer M, Cossarizza A, Franceschi C. Control of apoptosis by the cellular ATP level. FEBS Lett. 1996;378(2):107–110.
   PubMed Web of Science ®Google Scholar
• He L, Wang K-N, Zheng Y, Cao J-J, Zhang M-F, Tan C-P, Ji L-N, Mao Z-W. Cyclometalated iridium(iii) complexes induce mitochondria-derived paraptotic cell death and inhibit tumor growth in vivo. Dalton Trans. 2018;47(20):6942–6953.
   PubMed Web of Science ®Google Scholar
• Marchi S, Giorgi C, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Missiroli S, Patergnani S, Poletti F, et al. Mitochondria-ros crosstalk in the control of cell death and aging. J Signal Transduct. 2012;2012:329635,
   PubMedGoogle Scholar
• Daugas E, Nochy D, Ravagnan L, Loeffler M, Susin SA, Zamzami N, Kroemer G. Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett. 2000;476(3):118–123.
   PubMed Web of Science ®Google Scholar
• Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 1999;397(6718):441–446.
   PubMed Web of Science ®Google Scholar
• Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H, et al. DNA binding is required for the apoptogenic action of apoptosis inducing factor. Nat Struct Biol. 2002;9(9):680–684.
   PubMedGoogle Scholar
• Mariño G, Kroemer G. Mechanisms of apoptotic phosphatidylserine exposure. Cell Res. 2013;23(11):1247–1248.
   PubMed Web of Science ®Google Scholar