br Results HC significantly altered growth
Results: HC9 significantly altered growth of breast cancer cell lines, MCF-7 and MDA MB-231. It blocked the Thonzonium Bromide progression at S phase in MCF-7 by up regulating the expression of p53, p21 and p16 proteins. In MDA MB-231, HC9 induced G1 phase arrest by up regulating the expression of p53, p21 and pRb proteins with simultaneous decrease in ppRb. It significantly reduced migration and invasion in both the cell lines, accompanied by decrease in the expression of MMP-2/9, HIF-1α and VEGF. HC9 decreased the expression of inflammatory markers (NF-қB, COX-2), and modulated the expression of chromatin modulators (SMAR1 and CDP/Cux) in both MCF-7 and MDA MB-231.
Conclusions: HC9 exhibited potent anticancer activity against breast cancer cells, thereby warranting further pre-clinical and clinical studies in future.
Breast cancer is the second leading cause of cancer death in women worldwide and the first leading cause of death in Indian women (Torre et al., 2015). Although conventional therapies are eﬀective and target specific, they are associated with serious adverse events including drug resistance (Holohan et al., 2013). During the last decade there has been an upsurge in the use of medicinal plants and traditional herbal for-mulations as adjunct to cancer therapy (Sakarkar and Deshmukh, 2011). These herbal remedies not only exhibit anticancer activity but they also boost up the immune system (Murunikkara, and Rasool, 2014; Jeba et al., 2011). These remedies have been reported to reduce the chemotherapy associated toxicity and side-eﬀects as well as improve
HC9 is based upon an Ayurvedic formulation, Stanya Shodhana Kashaya (SSK), formulated on Stanyashodhana gana, explained by Charaka in Charakasaṃhita (Charakasaṃhita Sutrasthana 4:18) and mentioned in other texts as well (Hebbar, 2015). The name is derived from the words, Stanya, meaning “breast milk”, and sodhana, meaning “refining” or “purification” (Wisdom Library, 2012). The formulation is prescribed by Ayurvedic practitioners to cleanse and detox breast milk in mother and also for relieving the milk thickness caused due to the plugging of milk ducts. It is also given for treating other clinical con-ditions such as indigestion, diarrhea, vomiting, asthma, etc. (Bhutya, 2011). HC9 is composed of equal ratios of nine diﬀerent medicinal
∗ Corresponding author. E-mail address: [email protected] (R. Kaul-Ghanekar).
S. Suryavanshi, et al.
plants that include Picrorhiza kurroa Royle ex Benth. (Kutaki) (root), Cyperus rotundus L. (Musta) (rhizome), Zingiber oﬃcinale Roscoe (Sunthi) (bark), Cedrus deodara (Roxb. ex D.Don) G.Don (Devdar) (root), Tinospora cordifolia (Willd.) Miers (Gulvel) (stem), Holarrhena antidysenterica (Roth) Wall. ex A.DC. (Indrajav) (seed), Swertia chirata Buch.-Ham. ex Wall. (Kadechirai) (whole plant), Cissampelos pareira L. (Patha) (root) and Hemidesmus indicus (L.) R. Br. ex Schult. (Anantmul) (root). HC9 diﬀers from SSK by having one ingredient [Marsdenia te-nacissima (Roxb.) Moon (Murva)] less due to unavailability of the plant material, which is mostly found in tropical hilly tracts of peninsular India and Vindhya ranges as well as lower Himalayan tracts (National Medicinal Plants Board, 2008). Moreover, Murva is a controversial drug and 11 plants are considered with same name in diﬀerent parts of India. It is also known as “Sandigdha dravays”, a term used for medicinal plants having various sources (Nayak and De, 2014; Tiwari et al., 2018). All the medicinal plants in the formulation have reported ac-tivity against diﬀerent types of cancers.
Previously, we have reported that HC9 formulation exhibited ex-cellent antioxidant potential and significantly reduced the viability of breast cancer cell lines (MCF7 and MDA MB231) without aﬀecting the viability of the non-cancerous breast cell line (MCF-10A) (Suryavanshi et al., 2011). HC9 was phytochemically standardized with respect to the marker compounds present in its individual plant materials (Suryavanshi et al., 2014). Compared to the individual plant compo-nents, the whole formulation of HC9 significantly reduced the viability of breast cancer cells without killing the non-cancerous cells (Suryavanshi et al., 2014). HC9 was further found to be safe in Swiss albino mice with no toxic or adverse eﬀect based on the acute and sub-acute toxicity studies (Suryavanshi et al., 2015).