Cutaneous squamous cell carcinoma (cSCC) is a type of malignant skin tumor derived from epidermal Malpighian cells. Photodynamic therapy is regarded as a crucial method in oncology. Hypocrellin A (HA), an efficient natural photosensitizer, has been reported to exert excellent light induced antiviral, antimicrobial and anticancer activity through mediating multiple signaling pathways. The purpose of the present study is to examine the effects of HA united red light irradiation on human squamous carcinoma A431 cells and further reveal the underlying regulatory mechanisms. The results showed that synergistic treatment of HA and red light irradiation inhibited cell proliferation and induced cell apoptosis and autophagy. Moreover, HA united red light irradiation caused a significant accumulation of reactive oxygen species (ROS), and induced the activation of c-Jun NH 2 terminal kinases (JNKs) which was inhibited by the antioxidant N-Acetyl-cysteine (NAC). Furthermore, HA united red light irradiation activated the nuclear factor-kappa B (NF-κB) pathway, and inhibition of NF-κB activity exacerbated HA united red light irradiation-induced apoptosis but suppressed cell autophagy. In addition, the inhibition of autophagy promoted HA united red light irradiation-induced apoptosis and facilitated the NF-κB activity. Over all, our results revealed that HA united red light irradiation could inhibit A431 cell proliferation by inducing apoptosis and autophagy via the activation of the ROS mediated JNK and NF-κB pathways, providing prospective for HA as a potential therapeutic for the treatment of cSCC.

中文翻译：

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抑制ROS-NF-κB依赖性自噬增强了Hypocrellin A联合LED红光诱导的鳞状癌A431细胞凋亡。

皮肤鳞状细胞癌（cSCC）是一种类型的恶性皮肤肿瘤，起源于表皮的Malpighian细胞。光动力疗法被认为是肿瘤学中的关键方法。Hypocrellin A（HA）是一种有效的天然光敏剂，据报道可通过介导多种信号传导途径发挥出色的光诱导抗病毒，抗微生物和抗癌活性。本研究的目的是检查HA联合红光照射对人鳞癌A431细胞的影响，并进一步揭示其潜在的调控机制。结果表明，HA和红光的协同处理抑制细胞增殖，诱导细胞凋亡和自噬。此外，HA联合红光照射导致活性氧（ROS）大量积累，并诱导被抗氧化剂N-乙酰半胱氨酸（NAC）抑制的c-Jun NH 2末端激酶（JNKs）的激活。此外，HA联合红光辐照激活了核因子-κB（NF-κB）途径，抑制NF-κB活性加剧了HA联合红光辐照诱导的细胞凋亡，但抑制了细胞自噬。此外，自噬的抑制促进了HA联合红光照射诱导的细胞凋亡，并促进了NF-κB活性。总体而言，我们的结果表明，HA联合红光照射可通过激活ROS介导的JNK和NF-κB途径来诱导凋亡和自噬，从而抑制A431细胞增殖，为HA作为治疗cSCC的潜在疗法提供了前景。