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Published on: March 6, 2019
Herbal Melanin Inhibits Real-Time Cell Proliferation, Downregulates Anti-Apoptotic Proteins and Upregulates
Jothi Ramalingam Rajabathar1, Hamad Al-Lohedan1, Selvaraj Arokiyaraj2
1Surfactants Research Chair, Chemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Abstract:
Background and Objectives: Cancer is the second-most-important deadly disease in the world, leading to severe socioeconomic consequences and posing a public threat. Consequently, breast and colorectal cancers are significant cancer types that affect women and men more commonly, respectively. Treatment failure or recurrent diseases frequently occur due to resistance, in addition to the side effects of the currently available anticancer agents. Therefore, in this study, herbal melanin anticancer activity was investigated against human breast adenocarcinoma (MDA-MB-231) and human colorectal (HCT 116) cell proliferation and the expression of downregulated anti-apoptotic proteins and upregulated pro-apoptotic p53. Materials and Methods: MDA-MB-231 and HCT 116 cells were monitored for their real-time proliferation properties using Xcelligence. Herbal melanin of various concentrations significantly inhibited MDA-MB-231 and HCT 116 cell proliferation. Then, the expression of proapoptotic and anti-apoptotic proteins such as p53, Bcl-2 and Bcl-xl was studied using Western blotting. Results: The Bcl-2 and Bcl-xl expressions were downregulated, while the p53 expression was upregulated after treatment with herbal melanin. Similarly, the expression of apoptotic proteins such as Bcl-2, Bcl-xl, XIAP, Survivin, Bid, Bax, p53, Cytochrome C, PARP genes and mRNA was studied after herbal melanin treatment using real-time PCR, which revealed the downregulation of Bcl-2, Bcl-xl, XIAP and Survivin and the upregulation of Bid, Bax, p53, Cytochrome C and PARP apoptotic protein expression. Also, caspase 3 and 9 expressions were monitored after the treatment with herbal melanin, which revealed the upregulation of both the MDA-MB-231 and HCT 116 cell types. Conclusions: Overall, herbal melanin can be used as an alternative anticancer agent against the MDA-MB-231 and HCT 116 cell types.
Insights
Herbal melanin shows anticancer activity by inhibiting breast and colorectal cancer cell proliferation. It modulates apoptotic protein expression, suggesting potential as an alternative cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Cancer remains a leading global cause of death, with breast and colorectal cancers being highly prevalent.
- Current anticancer treatments face challenges like drug resistance and severe side effects.
- There is a need for novel, effective, and safer therapeutic agents.
Purpose of the Study:
- To investigate the anticancer potential of herbal melanin against human breast adenocarcinoma (MDA-MB-231) and colorectal (HCT 116) cancer cells.
- To analyze the effects of herbal melanin on the expression of key apoptotic and anti-apoptotic proteins.
- To evaluate herbal melanin as a potential alternative anticancer agent.
Main Methods:
- Real-time cell proliferation monitoring using Xcelligence assays for MDA-MB-231 and HCT 116 cell lines.
- Western blotting to assess the expression levels of proteins such as p53, Bcl-2, and Bcl-xl.
- Real-time PCR to examine the gene and mRNA expression of various apoptotic markers, including XIAP, Survivin, Bid, Bax, Cytochrome C, and PARP.
- Monitoring caspase 3 and 9 expression post-treatment.
Main Results:
- Herbal melanin significantly inhibited the proliferation of both MDA-MB-231 and HCT 116 cancer cells in a dose-dependent manner.
- Treatment with herbal melanin led to the downregulation of anti-apoptotic proteins (Bcl-2, Bcl-xl, XIAP, Survivin) and upregulation of pro-apoptotic proteins (p53, Bid, Bax, Cytochrome C, PARP).
- Herbal melanin induced the activation of caspases 3 and 9, key executioners of apoptosis, in both cancer cell types.
Conclusions:
- Herbal melanin demonstrates significant anticancer activity against human breast and colorectal cancer cell lines.
- The mechanism involves the induction of apoptosis through modulation of key apoptotic and anti-apoptotic protein pathways.
- Herbal melanin holds promise as a potential alternative therapeutic agent for breast and colorectal cancers.
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