Non-polar compounds of Persian Gulf sea cucumber Holothuria parva selectively induce toxicity on skin mitochondria isolated from animal model of melanoma

Abstract

Purpose: Melanoma is a highly aggressive and deadly cancer with a poor prognosis given its drug resistance. A defect in apoptosis is one of the key mechanisms that contribute to drug resistance in Melanoma. An important sea marine animal is the Holothuria parva, also known as the sea cucumber, which has various pharmacological activities. Compounds obtained from sea cucumbers have shown to have anticancer activity through induction of apoptosis singling.

Materials and methods: In the present study, selective toxicity and apoptotic effect of three extracts of H. parva were assessed on skin mitochondria isolated from mouse animal models of melanoma. The mitochondria was isolated from melanoma cells via differential centrifuges and treated with various concentrations (250, 500 and 1000 µg/ml) of metanolic, diethyl ether and n-hexane extracts of H. parva.

Results: All the applied concentrations (250, 500 and 1000 µg/ml) of three extracts of H. parva increased the reactive oxygen species (ROS) generation only in the skin mitochondria isolated from melanoma cells group (in comparison to the control group). Additionally, all three extracts (250, 500 and 1000 µg/ml) induced swelling within the mitochondria, the collapse of the mitochondrial membrane potential (MMP) and the release of cytochrome c from the mitochondria. Flow-cytometry analysis demonstrated that n-hexane and diethyl ether extracts of H. parva selectively and progressively induced apoptosis only on melanoma but not healthy control skin cells group.

Conclusions: Given these results, the potentially bioactive compounds found in H. parva render it a strong candidate for further research in molecular identification and confirmatory in vivo studies. Clinical trials are also warranted in the general process of novel drug discovery for the treatment of melanoma cancer.

Keywords:

• Holothuria parva
• melanoma
• apoptosis
• mitochondria
• reactive oxygen species

Acknowledgements

The results presented in this article were partly extracted from Dr. Yalda Arast’s thesis, PhD graduate of Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The thesis was performed under the supervision of Prof. Jalal Pourahmad This research was financially supported by Iran National Science Foundation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The investigation was financially supported by research grant [grant number 6046] from the Shahid Beheshti University of Medical Sciences, Deputy of Research, Tehran, Iran.