New insights into therapeutic activity and anticancer properties of curcumin

Figures & data

Figure 1 Effect of curcumin on various cellular pathways of different types of cancer.

Abbreviations: MMP, matrix metalloproteinase; COX, cyclooxygenase.

Table 1 Different pathways of various cancers regulated by curcumin as an adjuvant

Serial no.	Types of cancer	Pathways affected by curcumin		Drugs normally given in combination	References
		Upregulated	Downregulated
1.	Breast cancer	p53-dependent BAX pathway, mitotic spindle disruption	LOX pathway, MMP-9 pathway, and metastasis	Doxorubicin, brentuximab, carboplatin, vinblastine	^Citation8,Citation59,Citation63,Citation89^–^Citation95
2.	Lung cancer	P21/Apaf/caspase 9 pathway of apoptosis	STAT1, NAT pathway, and FPTase-mediated cell growth	Gemcitabine, topotecan, pertuzumab	^Citation8,Citation59,Citation63,Citation74,Citation95^–^Citation99
3.	Colorectal cancer	JNK, p38MAPK pathway, TRAIL-induced apoptosis	Notch1 pathway, COX-2-mediated cell renewal	5-Fluorouracil, trastuzumab	^Citation8,Citation59,Citation62,Citation63,Citation99^–^Citation105
4.	Leukemia	Caspase-3 and -8, P27 KIP-1 pathway	Cyclin D and NF-κB-mediated cell division	Methotrexate, bosutinib	^Citation8,Citation59,Citation63,Citation106^–^Citation110, ^Citation111
5.	Prostate cancer	BIM-mediated apoptosis, BAX pathway	NF-κB-induced growth, AKT pathway, and cell division	Vinorelbine, cobimetinib	^Citation8,Citation59,Citation62,Citation112^–^Citation117, ^Citation118
6.	Cervical and uterine cancers	BAD-mediated apoptosis	ETS-1 production, NF-κB, and AP-1 pathways	Cisplatin, carboplatin	^Citation8,Citation59,Citation62,Citation119^–^Citation123
7.	Oral cancer	P450 pathway and apoptosis	COX-2 pathway and cell renewal	Radiation, faslodex	^Citation8,Citation59,Citation62,Citation80,Citation124,Citation125
8.	Lymphoma	BAX and BIM pathways	JAK-STAT, tyrosine kinase, and AKT pathways	Doxorubicin, methotrexate	^Citation8,Citation59,Citation62,Citation113, ^Citation126^–^Citation128,Citation111

Abbreviations: COX, cyclooxygenase; MMP, matrix metalloprotease; LOX, lipoxygenase; TRAIL, TNF-related apoptosis-inducing ligand; NAT, arylamine N-acetyltransferase; NF-κB, nuclear factor-kappa B; AP-1, activating protein1; STAT, signal transducers and activators of transcription; FPTase, farnesyl protein transferase; JAK, janus kinase; JNK, c-jun N-terminal kinase; MAPK, mitogen-activated protein kinase.

Table 2 Different pathways of various cancers regulated by curcumin alone

Types of cancers	Signaling pathways effected	References
Breast cancer	Upregulation of p53 and BAX, cyclin D1, and mitochondrial release of cytochrome c	^Citation5,Citation8,Citation129
Lymphoma	Inhibits both NF-κB and STAT3 activation, thereby inhibiting BCL-2, BCL-xL, cFLIP, XIAP, c-IAP1, survivin, c-MYC, and cyclin D1	^Citation5,Citation8,Citation130,Citation131
Prostate cancer	Upregulation of the expression of TRAIL-R1/DR4, TRAILR2/DR5, BAX, BAK, p21/WAF1, and p27/KIP-1	^Citation5,Citation8,Citation132
Cervical cancer	Upregulation of proapoptotic BAX, AIF, release of cytochrome c, and caspase-3 and -9 activities Downregulation of antiapoptotic BCL-2, BCL-xL	^Citation5,Citation8,Citation133
Leukemia	Inhibition of serine/threonine protein kinase and AKT pathway	^Citation5,Citation8,Citation111
Lung cancer	Activation of caspase-3 and caspase-9	^Citation5,Citation8,Citation134
Colorectal cancer	Downregulation of COX-2 and inhibition of PGE2 synthesis	^Citation5,Citation105

Table 3 Recent clinical trials using curcumin as an anticancer agent

Serial no.	Cancer type	Trial condition	Trial	Location	Identifier no./ref*	Last updated
1.	Breast cancer	Completed	Curcumin for the prevention of radiation-induced dermatitis in breast cancer patients	University of Rochester	NCT01042938	2013
2.	Cervical cancer	Completed	Effect of curcumin addition to standard treatment on tumur-induced inflammation in endometrial carcinoma	University Hospital, Gasthuisberg	NCT02017353	2016
3.	Pancreatic cancer	Completed	Trial of curcumin in advanced pancreatic cancer	M.D. Anderson Cancer center	NCT00094445	2014
4.	Head and neck cancer (including oral cancer)	Completed	Curcumin biomarker trial in head and neck cancer	Louisiana State University Health Sciences Center	NCT01160302	2016
5.	Colon cancer	Completed	Curcumin for the prevention of colon cancer	University of Michigan Cancer Center	NCT00027495	2013
6.	Prostate cancer	Completed	Radiosensitizing and radioprotective effects of curcumin in prostate cancer	Shahid Beheshti University of Medical Sciences	NCT01917890	2016
7.	Breast cancer	Completed	Prophylactic topical agents in patients with non-inflammatory breast cancer or breast cancer in situ (Curcumin-II)	National Cancer Institute (NCI)	NCT02556632	2016
8.	Gastric cancer	Ongoing	Curcumin in preventing gastric cancer in patients	National Cancer Institute (NCI)	NCT02782949	2016
9.	Colon cancer	Ongoing	Curcumin in combination with 5-FU for colon cancer	Baylor Research Institute	NCT02724202	2016
10.	Cervical cancer	Ongoing	Topical curcumin for precancer cervical lesions	Emory University	NCT02944578	2016
11.	Lymphoma	Ongoing	Curcumin and cholecalciferol in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma	National Cancer Institute (NCI)	NCT02100423	2016
12.	Breast cancer	Ongoing	Docetaxel with or without curcumin in treating patients with breast cancer	Centre Jean Perrin	NCT00852332	2016
13.	Lung cancer	Ongoing	Cohort trial of curcumin plus tyrosine kinase inhibitors (TKIs) for EGFR-mutant advanced NSCLC	Lady Davis Institute	NCT02321293	2016
14.	Breast cancer	Ongoing	Phase-II study of curcumin vs placebo for chemotherapy-treated breast cancer patients undergoing radiotherapy	Emory University	NCT01740323	2016

Note:

* www.clinicaltrials.gov.

Abbreviations: 5-FU, 5-fluorouracil; NSCLC, non-small-cell lung carcinoma.

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