Mehraj Umar, Mir Irfan Ahmad, Hussain Mahboob Ul, Alkhanani Mustfa, Wani Nissar Ahmad, Mir Manzoor Ahmad
Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, India.
Department of Biotechnology, School of Biological Sciences, University of Kashmir, Srinagar, India.
Front Oncol. 2022 Jul 6;12:938052. doi: 10.3389/fonc.2022.938052. eCollection 2022.
Doxorubicin is a commonly used chemotherapeutic agent to treat several malignancies, including aggressive tumors like triple-negative breast cancer. It has a limited therapeutic index owing to its extreme toxicity and the emergence of drug resistance. As a result, there is a pressing need to find innovative drugs that enhance the effectiveness of doxorubicin while minimizing its toxicity. The rationale of the present study is that combining emerging treatment agents or repurposed pharmaceuticals with doxorubicin might increase susceptibility to therapeutics and the subsequent establishment of improved pharmacological combinations for treating triple-negative breast cancer. Additionally, combined treatment will facilitate dosage reduction, reducing the toxicity associated with doxorubicin. Recently, the third-generation retinoid adapalene was reported as an effective anticancer agent in several malignancies. This study aimed to determine the anticancer activity of adapalene in TNBC cells and its effectiveness in combination with doxorubicin, and the mechanistic pathways in inhibiting tumorigenicity. Adapalene inhibits tumor cell growth and proliferation and acts synergistically with doxorubicin in inhibiting growth, colony formation, and migration of TNBC cells. Also, the combination of adapalene and doxorubicin enhanced the accumulation of reactive oxygen species triggering hyperphosphorylation of Erk1/2 and caspase-dependent apoptosis. Our results demonstrate that adapalene is a promising antitumor agent that may be used as a single agent or combined with present therapeutic regimens for TNBC treatment.
阿霉素是一种常用的化疗药物，用于治疗多种恶性肿瘤，包括三阴性乳腺癌等侵袭性肿瘤。由于其极高的毒性和耐药性的出现，其治疗指数有限。因此，迫切需要找到创新药物，在将阿霉素毒性降至最低的同时提高其疗效。本研究的基本原理是，将新兴治疗药物或重新利用的药物与阿霉素联合使用，可能会增加对治疗的敏感性，并随后建立用于治疗三阴性乳腺癌的改良药物组合。此外，联合治疗将有助于减少剂量，降低与阿霉素相关的毒性。最近，第三代维甲酸阿达帕林被报道为几种恶性肿瘤中的一种有效抗癌药物。本研究旨在确定阿达帕林在三阴性乳腺癌细胞中的抗癌活性及其与阿霉素联合使用的有效性，以及抑制肿瘤发生的机制途径。阿达帕林抑制肿瘤细胞生长和增殖，并与阿霉素协同作用，抑制三阴性乳腺癌细胞的生长、集落形成和迁移。此外，阿达帕林和阿霉素的联合使用增强了活性氧的积累，引发了Erk1/2的过度磷酸化和半胱天冬酶依赖性凋亡。我们的结果表明，阿达帕林是一种有前途的抗肿瘤药物，可作为单一药物或与目前的治疗方案联合用于三阴性乳腺癌的治疗。
