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Molecules 2020, 25, 4102 12 of 22 5.3. Curcumins Curcumin (CU) is a plant-based therapeutic compound isolated from rhizome of Curcuma longa of the Zingiberaceae family. Curcuminoid is one of the most extensively studied plant-derived bioactive compounds [114]. Since the 1980s, the photobiological potential of CU was of great interest [115,116], and studies described CU as a desirable, highly promising photosensitiser [115,117–121]. The foremost property of CU is that it is biologically safe even at higher doses, and it can be easily produced on a large scale [117,122]. The photobleaching analysis reported the degradation profile of curcumin derivatives and its ability to produce singlet oxygen species [123]. CU was characterised by an absorption spectrum of 300–500 nm with a high extinction coefficient. This suggests that CU can induce a strong phototoxic reaction even at lower concentrations [124–126]. Curcumin is considered as a potential anticancer agent and inhibits cancer cell proliferation in breast, lung, colon, kidney, ovary, and liver cancers [114]. The in vitro and in vivo anticancer activity of curcumin has been proved by inhibition of various transcription factors such as NF-κB, AP-1, VEGF, iNOS, COX-2, 5-LOX, MMP-2, MMP-9 and IL-8, which are mainly responsible for angiogenesis and tumour growth [127,128]. The administration of curcumin significantly reduced the expression of the CDK4/cylin D1 complex by inhibiting p53 expression and causing the apoptotic process by inducing ROS generation. Furthermore, the enhanced antitumour activity was noted after UVB irradiation of curcumin by caspase activation on HaCaT (human keratinocyte cell) cells. It was also efficient against MCF-7 breast cancer cells at 30 J/cm2 [77,78]. These data suggested that curcumin may act as a potent anticancer agent by preventing cancer progression, migration and invasion [129–131]. Dovigo et al. [132] found the light absorption ability of CU in the range of 300 and 500 nm with a maximum absorption at 430 nm, which might support its usage as a PS. The ROS-inducing and anticancer ability of CU makes it a potent candidate as a natural PS [133]. Nevertheless, Chan and Wu [134] observed that the photoactive nature of CU on human epidermal A431 carcinoma cells and the higher amount of CU also affect the irradiation penetration [132,134,135]. The irradiation of CU under a 290–320 nm UVB light source with the fluence of 100 mJ/cm2 induced apoptosis in HaCaT keratinocyte cells [78]. Based on the above reports, CU can be used as a natural PS, and it can achieve high efficacy at a low concentration when combined with PDT. The existing PDT and photoactive reports on CU suggest that CU can be used as a potential and promising natural PS in PDT. In conclusion, CU can be a potent photosensitiser in the treatment of cancer and skin infections. Therefore, investigating the photodynamic potential of CU derivatives in terms of higher absorption and extinction coefficient will contribute to the increased efficacy of photodynamic toxicity. 5.4. Alkaloids Alkaloids, a diverse secondary metabolites group from higher plants, contain a heterocyclic structure with a nitrogen atom in the ring [136]. Nitrogen-containing alkaloids are normally photoactive in nature, e.g., quinine and cinchonamine. The alkaloids were reported for many significant properties, such as analgesic and anticancer activity [136–139]. The alkaloids camptothecin and vinblastine are few alkaloids were successfully utilised as chemotherapeutic drugs [138,140]. The anticancer activity of alkaloids was proved by different studies by means of disturbing tumour progression by induction of cell cycle arrest at the G1 or G2/M phases, regulating cyclin-dependent kinase (CDK) and promoting apoptosis as well as autophagy in tumour cells. Furthermore, these compounds induce apoptosis by regulating Bax, Bcl-2, Bcl-xL, NF-κB and various caspase proteins [140–143]. In addition, the combination of alkaloids with chemotherapeutic drugs and irradiation also enhanced the biological activities [144,145]. Furthermore, alkaloids induce the formation of intracellular ROS in cancer cells, which leads to the destruction of cancer cell metabolism [140–143]. The photochemically best-known alkaloid is berberine; Luiza Andreazza et al. [146], Bhattacharyya et al. [147] and Inbaraj et al. [81] reported the antitumour activity of berberine upon UV and blue light irradiation. The irradiation of berberine at 410 nm proved to be effective in controlling brain cancer cell growth [146]. Beta-carboline and harmine are also a noticeable alkaloid with a photoactive nature and are reported to produce aPDF Image | Role of Photoactive Phytocompounds in Photodynamic Therapy of Cancer
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