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Multiple myeloma (MM) is an incurable cancer that is characterized by malignant plasma cell proliferation. Approximately 10% of all blood cancers are MM, and there is no standard curative therapy. In this work, we intended to synthesize, characterize, and assess the anticancer effects of selenium/chitosan/polyethylene glycol–carvacrol nanocomposites (SCP‐Car‐NCs) on MM U266 cells in vitro. Various characterization techniques were used to characterize the synthesized SCP‐Car‐NCs. Several in vitro free radical scavenging experiments were conducted to test the ability of synthesized SCP‐Car‐NCs to scavenge the different free radicals. The cytotoxicity of SCP‐Car‐NCs was assessed on Vero and U266 cells using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay. By using various fluorescence staining techniques, the amount of reactive oxygen species (ROS) generation, MMP, and apoptosis were measured. Using commercial test kits, the levels of oxidative stress and apoptotic biomarkers in control and treated U266 cells were assessed. The highest peak in the UV spectral analysis was found to be at 271 nm, demonstrating the development of SCP‐Car‐NCs. Fourier transform infrared analysis showed that the synthesized SCP‐Car‐NCs contained a variety of stretching and bonding. The X‐ray diffraction study confirmed the crystallinity of SCP‐Car‐NCs. The dynamic light scattering analysis showed that the SCP‐Car‐NCs had an average size of 171 nm. The different free radicals, such as the 2,2‐diphenyl‐1‐picrylhydrazyl, hydroxyl, and peroxyl radicals, were significantly scavenged by the SCP‐Car‐NCs. According to the MTT assay results, the SCP‐Car‐NCs decreased the viability of U266 cells while having no impact on the proliferation of Vero cells. The SCP‐Car‐NCs significantly boosted ROS production, decreased the MMP level, and promoted apoptosis, as evidenced by the fluorescence staining experiments. In U266 cells treated with SCP‐Car‐NCs, the level of thiobarbituric acid reactive substances increased while superoxide dismutases and glutathione levels were reduced. In the SCP‐Car‐NCs treated U266 cells, it was found that the Bax, caspase‐3, and −9 activities had increased while the Bcl‐2 level had decreased. In conclusion, our findings show that SCP‐Car‐NCs treatment reduced the viability and increased apoptosis in the U266 cells, providing a new insight on SCP‐Car‐NCs' potential for usage in the future to treat MM. [ABSTRACT FROM AUTHOR]

Patients with cervical cancer have a significant risk of tumor recurrence and metastasis. The discovery of effective treatments for cervical cancer is urgently needed. Poly(lactic-co-glycolic acid) (PLGA) was recently discovered to offer a promising therapeutic drug carrier. Hence, we developed dual-loaded PLGA nanoparticles (NPs) as a drug carrier to combat this problem with current chemotherapeutic drugs for cervical cancer. We engineered PLGA NPs with epidermal growth factor (EGF) functionalization and co-loaded them with SN-38 and perfluorocarbon (PC) to treat cervical cancer selectively. Cell counting kit-8 test results reveal that newly fabricated NPs effectively induce cell proliferation in cervical cancer cells. Further, flow cytometry, Hoechst 33342 staining and acridine orange and propidium iodide staining were used to determine the apoptosis of SN38/PC@EGF-PLGA NPs in HeLa and CaSki cells. And the release was pH-dependent when tested in vitro. Cervical cancer cells took up targeted SN38/PC@EGF-PLGA NPs at a greater rate than untargeted NPs. Furthermore, HeLa and CaSki cells were more sensitive to apoptosis induction and cell viability suppression when exposed to SN38/PC@EGF-PLGA NPs than nontargeted NPs. The findings of this study improve the exploration of SN38/PC@EGF-PLGA NPs in the new development of effective drug candidates for highly invasive cervical cancer in future. [ABSTRACT FROM AUTHOR]

• Structure design based on known anticancer drug. • New agents against non-small cell lung cancer. • Good bioactivity against both mutant and wild-type cancer cell lines. • New agents inducing apoptosis and arresting cell cycle. EGFR-TK pathway is of high importance for the treatment of non-small-cell lung cancers (NSCLC), and it will be challenging to develop anti-tumor drugs that could inhibit both EGFR wild-type and mutant tumor cells. Here, a series of icotinib derivatives containing 1,2,3-triazole moiety were designed and synthesized through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Preliminary CCK-8 assay showed that the prepared icotinib-1,2,3-triazole compounds such as a7 or a12 demonstrated potent in vitro antitumor activity against the NSCLC cells expressing both wild type EGFR and mutational EGFR. Further, the mechanism of action for compounds a7 and a12 induced NSCLC cells death was also detailed, and the results suggested a possible induced NSCLC cells death via inducing mitochondrial apoptosis and arresting cell cycle. Remarkably, the inhibition of EGFR by these icotinib derivatives was also studied. The results showed that compound a12 was a potent inhibitor for EGFR with IC 50 value of 1.49 μM. Combining these results, an EGFR inhibitor a12 represents a promising new anti-NSCLC candidate that could induce apoptosis and arrest cell cycle. [ABSTRACT FROM AUTHOR]

Abstract: A series of carbamate derivatives of 4′-demethylepipodophyllotoxin have been synthesized, and their cytotoxicities against several human cancer cell lines, including HeLa, A549, HCT-8, and HL-60 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-4′-Demethylepipodophyllotoxin 1-(4-nitrophenyl) piperazinyl carbamate (19) was found to be the most potent compound of those synthesized in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of Bax, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form. [Copyright &y& Elsevier]

Abstract: A series of 4β-amino-4′-O-demethyl-4-deoxypodophyllotoxin derivatives were synthesized, and their cytotoxicities against several human cancer cell lines, including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-N-(4-Nitrophenyl piperazinyl)-4′-O-demethyl-4-deoxypodophyllotoxin (11) was found to be the most potent synthesized compound in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form. [Copyright &y& Elsevier]