Combating breast cancer using combination therapy with 3 phytochemicals: Piperine, sulforaphane, and thymoquinone.
Despite the significant advances in screening methods for early diagnosis, breast cancer remains a global threat and continues to be the leading cancer diagnosed in women, requiring effective therapy. Currently, combination therapy has become the hallmark of breast cancer treatment due to the high incidence of tumor recurrence and disease progression after monotherapeutic treatments, including surgery, radiotherapy, endocrine therapy, and chemotherapy. Over the past decades, there has been considerable interest in studying the anticancer effect of bioactive phytochemicals from medicinal plants combined with these conventional therapies. The rationale for this type of therapy is to use combinations of drugs that work by different mechanisms, thereby decreasing the likelihood that cancer cells will develop resistance, and also reduce the therapeutic dose and toxicity of single treatments. Three agents have received great attention with regard to their anticancer properties: 1) piperine, a dietary phytochemical isolated from black pepper (Piper nigrum L.) and long pepper (Piper longum L.); 2) sulforaphane, an isothiocyanate mainly derived from cruciferous vegetables; and 3) thymoquinone, the active compound from black seed (Nigella sativa L.). This review focused on the combined effect of these 3 compounds on conventional cancer therapy with the objective of observing enhanced efficacy compared with single treatments. This review also highlights the importance of the nanoformulation of such bioactive phytochemicals that could enhance their bioavailability by providing an efficient targeted delivery system with a reduced systemic dose while resulting in a more efficient dosing at the target site.
Aumeeruddy MZ
,Mahomoodally MF
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Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy.
Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3'-di-indolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development.
Dandawate PR
,Subramaniam D
,Jensen RA
,Anant S
... -
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Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives.
Breast cancer is one of the most commonly diagnosed cancers around the globe and accounts for a large proportion of fatalities in women. Despite the advancement in therapeutic and diagnostic procedures, breast cancer still represents a major challenge. Current anti-breast cancer approaches include surgical removal, radiotherapy, hormonal therapy and the use of various chemotherapeutic drugs. However, drug resistance, associated serious adverse effects, metastasis and recurrence complications still need to be resolved which demand safe and alternative strategies. In this scenario, phytochemicals have recently gained huge attention due to their safety profile and cost-effectiveness. These phytochemicals modulate various genes, gene products and signalling pathways, thereby inhibiting breast cancer cell proliferation, invasion, angiogenesis and metastasis and inducing apoptosis. Moreover, they also target breast cancer stem cells and overcome drug resistance problems in breast carcinomas. Phytochemicals as adjuvants with chemotherapeutic drugs have greatly enhanced their therapeutic efficacy. This review focuses on the recently recognized molecular mechanisms underlying breast cancer chemoprevention with the use of phytochemicals such as curcumin, resveratrol, silibinin, genistein, epigallocatechin gallate, secoisolariciresinol, thymoquinone, kaempferol, quercetin, parthenolide, sulforaphane, ginsenosides, naringenin, isoliquiritigenin, luteolin, benzyl isothiocyanate, α-mangostin, 3,3'-diindolylmethane, pterostilbene, vinca alkaloids and apigenin.
Younas M
,Hano C
,Giglioli-Guivarc'h N
,Abbasi BH
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《RSC Advances》